rs234709

Positions:

• chr21-43066854-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000398165.8(CBS):​c.317-477G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.071 (1225 hom., cov: 16)
  • Failed GnomAD Quality Control
• Consequence: CBS ENST00000398165.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.628

Genes affected

CBS (HGNC:1550): (cystathionine beta-synthase) The protein encoded by this gene acts as a homotetramer to catalyze the conversion of homocysteine to cystathionine, the first step in the transsulfuration pathway. The encoded protein is allosterically activated by adenosyl-methionine and uses pyridoxal phosphate as a cofactor. Defects in this gene can cause cystathionine beta-synthase deficiency (CBSD), which can lead to homocystinuria. This gene is a major contributor to cellular hydrogen sulfide production. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBS	NM_000071.3	c.317-477G>A		intron_variant		ENST00000398165.8	NP_000062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBS	ENST00000398165.8	c.317-477G>A		intron_variant		1	NM_000071.3	ENSP00000381231	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 6202 AN: 86766 Hom.: 1224 Cov.: 16 FAILED QC

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.0424

Gnomad AMR AF: 0.0527

Gnomad ASJ AF: 0.0491

Gnomad EAS AF: 0.0118

Gnomad SAS AF: 0.0319

Gnomad FIN AF: 0.0165

Gnomad MID AF: 0.0260

Gnomad NFE AF: 0.0487

Gnomad OTH AF: 0.0629

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0715 AC: 6203 AN: 86792 Hom.: 1225 Cov.: 16 AF XY: 0.0688 AC XY: 2993 AN XY: 43520

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.0525

Gnomad4 ASJ AF: 0.0491

Gnomad4 EAS AF: 0.0118

Gnomad4 SAS AF: 0.0319

Gnomad4 FIN AF: 0.0165

Gnomad4 NFE AF: 0.0487

Gnomad4 OTH AF: 0.0618

Alfa AF: 0.327 Hom.: 1706

Asia WGS AF: 0.283 AC: 985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs234709; hg19: chr21-44486964;